Rensselaer Magazine Winter 2007-08 - "Closing the Stem Cell Gap" Page 4

Promising Advances

Rensselaer researchers also are helping to develop exciting new medical technologies using stem cells. Professor of Chemical and Biological Engineering Ravi Kane has developed a three-dimensional scaffold for implanting and releasing stem cells into the body. The device is akin to a man-made stem cell niche, fostering the growth and release of differentiating stem cells into the body similar to the natural niche that Ligon is studying.

To create the scaffold, Kane and his team transformed a polymer found in common brown seaweed into a device that could support the growth and release of stem cells. The scaffold degrades at a controlled rate. It is the hope of Kane and his team that the scaffold will be able to be surgically implanted in the body at the site of injury or source of a disease and then release healthy stem cells into the body as it degrades, repairing cellular damage.

Kane and his collaborators created the device from a material known as alginate, a complex carbohydrate found naturally in brown seaweed. When mixed with calcium, alginate gels into a rigid, three-dimensional mesh. Kane and his team encapsulated healthy neural stem cells in the mesh. Once the cells were successfully encapsulated, the research team developed a mechanism that would allow the cells to be released after implantation in the body.

The researchers utilized an enzyme called alginate lyase that eats away at alginate to release the stem cells. In order to control the degradation of the alginate scaffold, the researchers encapsulated varying amounts of alginate lyase into microscale beads, called microspheres, which were then encapsulated into the larger alginate scaffolds along with the stem cells. As the microspheres degraded, the alginate lyase enzyme was released into the scaffold and slowly began to eat away at its surface, releasing the healthy stem cells in a controlled fashion.

The microspheres also can be filled with more than just alginate lyase. “We can add drug molecules or proteins to the microspheres along with the alginate lyase that when released into the larger alginate scaffold could influence the fate of the encapsulated stem cells,” Kane says. “By adding these materials to the larger scaffold, we could direct the stem cells to become the type of mature differentiated cell that we desired, such as a neuron. This will prove very valuable for applications of stem cells in regenerative medicine.”

John Brunski, professor of biomedical engineering, focuses on developing better bone implants. Brunski is looking at how stem cells develop and interact with implants while they are still in their natural environment, the body. His lab is investigating how implants with different loading histories and different implant surfaces impact bone stem cells, with the ultimate goal to develop implants that foster stem cell development and speed the healing process.

Ravi Kane

“The gap from stem cell to cure is wide, and researchers have a lot of middle ground to fill in before stem cell therapies will be as common as other revolutionary advances in medicine like vaccines and antibiotics. “We need a foundation of knowledge before we can create these therapies.”

“The body relies on stem cells to differentiate into bone cells that can heal broken bone tissue,” Brunski says. “When doctors use a synthetic implant, they are looking to damage stem cells as little as possible. We are looking for types of implants that do no harm to these important stem cells, and which might actually trigger stem cells to differentiate into bone sooner, speeding the healing process.”

Previous studies have revealed that certain mechanical signals can actually activate bone stem cell differentiation and growth. Brunski is looking at how the mechanical loading of an implant may be controlled to guide stem cell differentiation. Along with a collaborative team of researchers at Rensselaer and at Stanford and the University of Montreal, he has developed specialized implants that were placed in mouse bones. Their studies have shown that varying the loading of the implant and the implant’s shape can significantly change the rate of stem cell growth around the implant.

“Implants that stimulate stem cells to heal bone are particularly important for the elderly,” Brunski says. “As a person gets older, stem cell production is reduced at places of healing, making the healing process painstakingly slow. If we can use implants that speed that process, we could greatly improve lives post-surgery.”

While many in the burgeoning world of biotechnology are working to develop medications that foster stem cells, Jonathan Dordick, the Howard P. Isermann ’42 Professor of Chemical and Biological Engineering, has developed a high-throughput screening platform that will help scientists develop drugs that both grow and kill stem cells in the body.

“New research is showing that some stem cells could be the precursor for cancer and the reason that cancer reappears after having been totally eradicated by chemotherapy,” Dordick says. “With this platform we may be able to rapidly screen new drug candidates that target and kill these cancer stem cells. Instead of going for the mature liver cell that spreads cancer, we can catch a liver stem cell before it can kick off cancer development.”

The device is a form of lab-on-a-chip that condenses many experiments onto one small device, increasing the speed and efficiency of modern scientific and medical research. The one developed by Dordick and his team allows them to prepare up to 1,000 stem cell samples that are as small as 20 nanoliters on one chemically modified slide — making it possible to complete 1,000 experiments at the same time.

The device will enable drug researchers to quickly screen thousands of small molecules (the basic element of many modern drugs) for their effects on the differentiation of stem cells. Once a molecule is found that has the desired impact on the stem cells, it can be isolated and further investigated by the lab.

With the number of Institute researchers and students working on stem cell projects likely to increase in the coming years, more breakthroughs like Dordick’s are sure to follow. The variables remain the funding and public support for further study. In the meantime, Rensselaer researchers forge ahead to the future. “Our scientists are filling a vital niche in the global scientific effort to develop medical therapies and new technologies using stem cells,” Palazzo says.

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Rensselaer (ISSN 0898-1442) is published in Spring, Summer, Fall, and Winter by the Office of Strategic Communications and External Relations, Rensselaer Polytechnic Institute, Troy, NY 12180-3590. Opinions expressed in these pages do not necessarily reflect the views of the editors or the policies of the Institute. ©2008 Rensselaer Polytechnic Institute.